Genome-wide Association Study Identifies <i>SORCS3</i> as a Novel Susceptibility Locus for Panic Disorder in the FinnGen Study
Bibliographic record
Abstract
Abstract Panic disorder is an anxiety disorder with poorly understood etiology. Although twin studies suggest modest heritability (∼40%), few genetic variants have been associated with it. We carried out a genome-wide association study in the Finnish longitudinal health register-based FinnGen study to identify genetic variants that predispose to panic disorder. FinnGen cases (N=3,549) were defined as individuals with an ICD-10 or ICD-9 lifetime diagnosis of panic disorder. Control subjects (N=159,869) were free of any psychiatric diagnoses. We identified a locus on chromosome 10q25.1 within SORCS3 that was significantly associated with panic disorder. The minor allele (T; frequency 21%) of the lead variant rs902306 increased the risk of panic disorder by 22% (OR=1.22, 95% CI=1.15-1.30, p-value=1.1×10 −10 ). We also investigated serum SORCS3 protein levels in 107 panic disorder cases with or without agoraphobia and 95 controls free of axis I psychiatric disorders collected at the Anxiety Disorders Outpatient Unit of the Max Planck Institute of Psychiatry. Serum SORCS3 levels were 41% higher in panic disorder cases compared to controls (ß=0.694, SE=0.141, p-value=8.7×10 −07 ). This finding replicated in 84 subjects from an independent German clinical panic disorder sample (ß=1.137, SE=0.532, p-value=0.04), but not in plasma samples of Finnish panic disorder patients from a biobank. Overall, SORCS3 is a novel panic disorder locus, which has previously been associated with other psychiatric and neurodevelopmental disorders. SORCS3 belongs to the sortilin family, with multiple functions related to brain plasticity. Characterization of its role in panic disorder will increase understanding of the neurobiological mechanisms involved in anxiety.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".